Immunomodulation is a developing segment of immunopharmacology. Immunomodulator compounds and compositions, as the name implies, are useful for modulating or regulating immunological functions in warm blooded animals. Immunomodulators may be immunostimulants for building up immunities to or initiate healing of certain diseases and disorders. Conversely, they may be immunoinhibitors or immunosuppressors for preventing undesirable immuno reactions of the body to foreign materials and autoimmue diseases.
Immunomodulators have been found to be useful for treating systemic autoimmue diseases, such as lupus erythematosus, as well as immunodeficiency diseases. Further, immunomodulators may be useful for immunotherapy of cancer or to prevent rejections of foreign organs or other tissues in transplants, e.g., kidney, heart or bone marrow.
Various immunomodulator compounds have been discovered including muramylic acid dipeptide derivatives, levamisole, niridazole, oxysuran, flagyl and others from the groups of interferons, interleukins, leukotrienes, corticosteroids and cyclosporins. Many of these compounds have been found, however, to have undesirable side effects and/or high toxicity. New immunomodulator compounds are therefore needed to provide a wider range of immunomodulator function for specific areas with a minimum of undesirable side effects.
In addition to work on immunomodulators, considerable research and resources have been devoted to oncology and antitumor measures including chemotherapy. While certain methods and chemical compositions have been developed which aid in inhibiting, remitting or controlling the growth of tumors, new methods and antitumor chemical compositions are needed.
In searching for new biologically active compounds, it has been found that some natural products and organisms are potential sources for chemical molecules having useful biological activity of great diversity. Marine sponges have proved to be such a source and a number of publications have been issued disclosing organic compounds derived from marine sponges including Scheuer, P. J. Ed., Marine Natural Products, Chemical and Biological Perspectives; Academic Press, New York, 1978, Vol. I, pp 175-240; Uemura et al., J. Am. Chem. Soc., 1985, 107, 4796-4798; Minale, L., et al., Fortschr. Chem. org. Naturst. 1976, 33, 1-72; Faulkner, D. J., Nat. Prod. Rep. 1987, 4, 539-576 and references cited therein.
The present invention has added to the arsenal of mmunomodulator and antitumor compounds by the discovery of new organic compounds possessing useful immunomodulator and antitumor activity isolated from extracts of the marine sponge Discodermia dissoluta.